The total synthesis of a veriety of compounds with demonstrated neurological activity is proposed. In particular we week to develop efficient synthetic procedures such that the target compounds will be available, via total synthesis, in sufficient quantities for detailed pharmacological evaluations. The general target structures are the pumiliotoxins, the gephyrotoxins, and pretazettine. Specifically we propose the total synthesis of the natural products pumiliotoxins II and III, gephyrotoxin, dihydrogephyrotoxin, and pretazettine. We moreover propose a rational program of analog preparation and testing which should afford basic structure-activity information, and perhaps yield compounds of greater activity that the natural materials. Our proposed synthetic routes are founded on dienamide Diels-Alder methodology which has been recently developed in our laboratory.